Platelet adherence to collagen: role of prostaglandin-thromboxane synthesis.
The effect of aspirin and indomethacin on adherence of human platelets to collagen was assessed by affinity chromatography on collagen/Sepharose. Studies were done using platelets from normal subjects and subjects ingesting aspirin. Blood was anticoagulated with EDTA, EGTA or citrate, and platelets were suspended in plasma or buffer after separation by centrifugation or gel filtration. The adherence to collagen of platelets from subjects ingesting 1200 mg aspirin per day decreased significantly (P less than 0.05 or below). A significant reduction in adherence also occurred after exposure to aspirin and indomethacin in vitro. The reduction in adherence was associated with inhibition of malondialdehyde (MDA) production and was unaffected by the presence of CP/CPK. Exposure of platelets to aspirin at 24 degrees C caused no impairment of adherence. The addition of 1.0 mM Ca++, 0.5 or 1.0 mM Mg++, or 1 mM arachidonic acid significantly diminished the inhibition of adherence by aspirin. Imidiazole had an effect on adherence opposite to that of aspirin. Changes in release of 14C-serotonin in general paralleled changes in adherence. The data suggest that aspirin and indomethacin impair but do not fully inhibit platelet adherence to collagen. Factors affecting this inhibitory activity in our system are the presence of plasma and availability of divalent cation. Platelet-collagen adhesion appears partly dependent upon prostaglandin-thromboxane synthesis and may be promoted by a different pathway that is stimulated by divalent cations and unaffected by inhibition of prostaglandin synthesis.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008875:Middle Aged; D010973:Platelet Adhesiveness / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis*; D012701:Serotonin / Q000097:blood; D013696:Temperature; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D007093:Imidazoles; D011453:Prostaglandins; D013931:Thromboxanes; D016718:Arachidonic Acid; D012701:Serotonin; D000244:Adenosine Diphosphate; C029899:imidazole; D003094:Collagen; D008274:Magnesium; D001241:Aspirin; D002118:Calcium; D007213:Indomethacin